title: Virtual screening for natural product inhibitors of HIV-1 integrase.
abstract: Since there is no human homolog of this enzyme, HIV-1 integrase (IN) represents a rational and important target for treating HIV infection and preventing AIDS. The 3D structure of full-length HIV-1 IN, either separately or in complex with its inhibitors, has been lacking. Thus, scarce information about the interactions between the HIV-1 IN and its inhibitors can be referenced. To more rationally design potent HIV-1 IN inhibitors, we have previously constructed a model of the full-length HIV-1 IN tetramer and a model of the protein-viral DNA complex, as well as the pharmacophore model of HIV-1 IN strand transfer inhibitors (INSTIs). In this paper, the pharmacophore model of INSTIs was used as a 3D query to screen the Traditional Chinese Medicine Database (TCMD). The hit compounds were further filtered by Lipinski's Rule of Five and docking study to refine the retrieved hits. Finally, 9 suitable ligands with similar structures belonging to the thioglycosides were selected. Subsequent molecular dynamics simulation showed that these compounds had interactions with HIV-1 IN binding site and their possible function as IN inhibitors was discussed.
authors.affiliation: Department of Chemistry, Basic Medical College of Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Shi-Kun
authors.initials: SK
authors.lastname: Ma
authors.forename: Ke-Zhu
authors.initials: KZ
authors.lastname: Wu
authors.forename: Ai-Xiu
authors.initials: AX
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013865:Thioglycosides / Q000737:chemistry
chemical_list: D004365:Drugs, Chinese Herbal; D019428:HIV Integrase Inhibitors; D008024:Ligands; D013865:Thioglycosides; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1